title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=781 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Zoledronic acid promotes osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation link: https://peerj.com/articles/12510 last-modified: 2021-12-16 description: Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ) is a severe complication of the long-term administration of BPs. The development of BRONJ is associated with the cell death of osteoclasts, but the underlying mechanism remains unclear. In the current study, the role of Zoledronic acid (ZA), a kind of bisphosphonates, in suppressing the growth of osteoclasts was investigated and its underlying mechanism was explored. The role of ZA in regulating osteoclasts function was evaluated in the RANKL-induced cell model. Cell viability was assessed by cell counting kit-8 (CCK-8) assay and fluorescein diacetate (FDA)-staining. We confirmed that ZA treatment suppressed cell viability of osteoclasts. Furthermore, ZA treatment led to osteoclasts death by facilitating osteoclasts ferroptosis, as evidenced by increased Fe2+, ROS, and malonyldialdehyde (MDA) level, and decreased glutathione peroxidase 4 (GPX4) and glutathione (GSH) level. Next, the gene expression profiles of alendronate- and risedronate-treated osteoclasts were obtained from Gene Expression Omnibus (GEO) dataset, and 18 differentially expressed genes were identified using venn diagram analysis. Among these 18 genes, the expression of F-box protein 9 (FBXO9) was inhibited by ZA treatment. Knockdown of FBXO9 resulted in osteoclasts ferroptosis. More important, FBXO9 overexpression repressed the effect of ZA on regulating osteoclasts ferroptosis. Mechanistically, FBXO9 interacted with p53 and decreased the protein stability of p53. Collectively, our study showed that ZA induced osteoclast cells ferroptosis by triggering FBXO9-mediated p53 ubiquitination and degradation. creator: Xingzhou Qu creator: Zhaoqi Sun creator: Yang Wang creator: Hui Shan Ong uri: https://doi.org/10.7717/peerj.12510 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Qu et al. title: Seroprevalence and lethality by SARS-CoV-2 in indigenous populations of Latin America and the Caribbean: a systematic review link: https://peerj.com/articles/12552 last-modified: 2021-12-16 description: BackgroundLatin America and the Caribbean (LAC) has presented some of the highest numbers of cases and deaths due to COVID-19 in the world. Even though indigenous communities represent 8% of the total population in this region, the impact of COVID-19 on this historically vulnerable population has only been briefly explored. Thus, this study aimed to estimate the seroprevalence and lethality attributable to SARS-CoV-2 in the indigenous population of LAC.MethodsA systematic review was conducted utilizing multiple databases (registry PROSPERO: CRD42020207862). Studies published in English, Spanish or Portuguese were selected between December 1st, 2019, and April 14th, 2021. The evaluation of the quality of the study was carried out utilizing the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A qualitative synthesis of the data analyzed was conducted following the MOOSE and PRISMA declarations.ResultsFifteen studies met the inclusion criteria. Eleven studies were carried out in a Brazilian population, three in a Mexican population, and one in a Colombian population. Four studies reported data about the seroprevalence of SARS-CoV-2 in indigenous populations of Brazil (range: 4.2–81.65%). Twelve studies reported lethality in indigenous people (eight in Brazil, three in Mexico, and one in Colombia). In Brazil, a lethality of 53.30% was described in a hospital setting and between 1.83% and 4.03% in community studies. In Mexico, the lethality of COVID-19 ranged between 16.5% and 19.9%. Meanwhile, in Colombia, a lethality of 3.41% was reported. Most studies were deemed to be of good quality.ConclusionsDespite COVID-19 affecting indigenous populations of LAC, there is limited evidence of the seroprevalence and lethality of the infection by SARS-CoV-2 in this population. Future investigations should ensure standardized methods that allow comparability among studies and ensure the precision of the results obtained. creator: Akram Hernández-Vásquez creator: Fabian Chavez-Ecos creator: Antonio Barrenechea-Pulache creator: Daniel Comandé creator: Guido Bendezu-Quispe uri: https://doi.org/10.7717/peerj.12552 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Hernández-Vásquez et al. title: Self-stigma and cognitive fusion in parents of children with autism spectrum disorder. The moderating role of self-compassion link: https://peerj.com/articles/12591 last-modified: 2021-12-16 description: BackgroundResearch shows that people with autism spectrum disorder and their families often experience social stigma. The internalization of social stigma can lead to the occurrence of self-stigma, understood as an internalized cognitive-affective self-directed and rigid process that results in individuals agreeing with stigmatizing opinions and applying them to themselves. Experiencing self-stigma can lead to a cognitive fusion with negative thoughts–especially those about oneself. Previous studies show that self-compassion reduces feelings of suffering, shame and self-stigma in a group of parents of children with autism spectrum disorder. The aim of this study was to test the relationship between self-stigma and cognitive fusion among parents of children with ASD. The moderating role of self-compassion as a protective factor was also verified.MethodsThe following questionnaires were used: Perceived Public Stigma Scale, Perceived Courtesy Stigma Scale, Self-Compassion Scale–Short Form, Cognitive Fusion Questionnaire, and Depression, Anxiety and Stress Scale. The study included 233 Polish parents of children with autism spectrum disorder (including 218 women).ResultsThe results showed a positive correlation between fusion and both affiliate (r = 0.31, p < 0.001) and public stigma (r = 0.33, p < 0.001). Fusion and self-compassion were significant predictors of affiliate stigma. Self-compassion moderated the relationship between fusion and depression (β = −0.11, p < 0.05) and the relationship between fusion and stress (β = −0.11, p < 0.05). Cognitive fusion with negative beliefs about oneself can contribute to self-stigma. Defusion-oriented actions are an opportunity to distance oneself from emerging thoughts and eliminate their negative consequences. Self-compassion manifests itself in a compassionate and accepting attitude towards oneself and improves the individual’s well-being. Actions taken to strengthen the indicated factors could contribute to a better quality of life of parents of children with ASD. creator: Anna Pyszkowska creator: Krzysztof Rożnawski creator: Zuzanna Farny uri: https://doi.org/10.7717/peerj.12591 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Pyszkowska et al. title: Ammonia-oxidizing bacterial communities are affected by nitrogen fertilization and grass species in native C4 grassland soils link: https://peerj.com/articles/12592 last-modified: 2021-12-16 description: BackgroundFertilizer addition can contribute to nitrogen (N) losses from soil by affecting microbial populations responsible for nitrification. However, the effects of N fertilization on ammonia oxidizing bacteria under C4 perennial grasses in nutrient-poor grasslands are not well studied.MethodsIn this study, a field experiment was used to assess the effects of N fertilization rate (0, 67, and 202 kg N ha−1) and grass species (switchgrass (Panicum virgatum) and big bluestem (Andropogon gerardii)) on ammonia-oxidizing bacterial (AOB) communities in C4 grassland soils using quantitative PCR, quantitative reverse transcription-PCR, and high-throughput amplicon sequencing of amoA genes.ResultsNitrosospira were dominant AOB in the C4 grassland soil throughout the growing season. N fertilization rate had a stronger influence on AOB community composition than C4 grass species. Elevated N fertilizer application increased the abundance, activity, and alpha-diversity of AOB communities as well as nitrification potential, nitrous oxide (N2O) emission and soil acidity. The abundance and species richness of AOB were higher under switchgrass compared to big bluestem. Soil pH, nitrate, nitrification potential, and N2O emission were significantly related to the variability in AOB community structures (p < 0.05). creator: Jialin Hu creator: Jonathan D. Richwine creator: Patrick D. Keyser creator: Lidong Li creator: Fei Yao creator: Sindhu Jagadamma creator: Jennifer M. DeBruyn uri: https://doi.org/10.7717/peerj.12592 license: https://creativecommons.org/publicdomain/zero/1.0/ rights: ©2021 Hu et al. title: Identification of evolutionary relationships and DNA markers in the medicinally important genus Fritillaria based on chloroplast genomics link: https://peerj.com/articles/12612 last-modified: 2021-12-16 description: The genus Fritillaria has attracted great attention because of its medicinal and ornamental values. At least three reasons, including the accurate discrimination between various Fritillaria species, protection and sustainable development of rare Fritillaria resources as well as understanding of relationship of some perplexing species, have prompted phylogenetic analyses and development of molecular markers for Fritillaria species. Here we determined the complete chloroplast (CP) genomes for F. unibracteata, F. przewalskii, F. delavayi, and F. sinica through Illumina sequencing, followed by de novo assembly. The lengths of the genomes ranged from 151,076 in F. unibracteata to 152,043 in F. przewalskii. Those CP genomes displayed a typical quadripartite structure, all including a pair of inverted repeats (26,078 to 26,355 bp) separated by the large single-copy (81,383 to 81,804 bp) and small single-copy (17,537 to 17,569 bp) regions. Fritillaria przewalskii, F. delavayi, and F. sinica equivalently encoded 133 unique genes consisting of 38 transfer RNA genes, eight ribosomal RNA genes, and 87 protein coding genes, whereas F. unibracteata contained 132 unique genes due to absence of the rps16 gene. Subsequently, comparative analysis of the complete CP genomes revealed that ycf1, trnL, trnF, ndhD, trnN-trnR, trnE-trnT, trnN, psbM-trnD, atpI, and rps19 to be useful molecular markers in taxonomic studies owning to their interspecies variations. Based on the comprehensive CP genome data collected from 53 species in Fritillaria and Lilium genera, a phylogenomic study was carried out with three Cardiocrinum species and five Amana species as outgroups. The results of the phylogenetic analysis showed that Fritillaria was a sister to Lilium, and the interspecies relationships within subgenus Fritillaria were well resolved. Furthermore, phylogenetic analysis based on the CP genome was proved to be a promising method in selecting potential novel medicinal resources to substitute current medicinal species that are on the verge of extinction. creator: Tian Zhang creator: Sipei Huang creator: Simin Song creator: Meng Zou creator: Tiechui Yang creator: Weiwei Wang creator: Jiayu Zhou creator: Hai Liao uri: https://doi.org/10.7717/peerj.12612 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Zhang et al. title: Ploidy level enhances the photosynthetic capacity of a tetraploid variety of Acer buergerianum Miq. link: https://peerj.com/articles/12620 last-modified: 2021-12-16 description: BackgroundPolyploidy plays an important role in plant breeding and has widespread effects on photosynthetic capacity. To determine the photosynthetic capacity of the tetraploid variety Acer buergerianum Miq. ‘Xingwang’, we compared the gas exchange parameters, chloroplast structure, chlorophyll contents, and chlorophyll fluorescence parameters between the tetraploid Acer buergerianum ‘Xingwang’ and the diploid ‘S4’. To evaluate the effects of genome duplication on the photosynthetic capacity of Acer buergerianum ‘Xingwang’, the transcriptomes of the autotetraploid ‘Xingwang’ and the diploid ‘S4’ of A. buergerianum were compared.MethodsThe ploidy of Acer buergerianum ‘Xingwang’ was identified by flow cytometry and the chromosome counting method. An LI-6800 portable photosynthesis system analyzer was used to assess the gas exchange parameters of the tetraploid variety ‘Xingwang’ and diploid variety ‘S4’ of A. buergerianum. We used a BioMate 3S ultraviolet-visible spectrophotometer and portable modulated fluorometer to measure the chlorophyll contents and chlorophyll fluorescence parameters, respectively, of ‘Xingwang’ and ‘S4’. Illumina high-throughput sequencing technology was used to identify the differences in the genes involved in the photosynthetic differences and determine their expression characteristics.ResultsThe single-cell DNA content and chromosome number of the tetraploid ‘Xingwang’ were twice those found in the normal diploid ‘S4’. In terms of gas exchange parameters, the change in stomatal conductance, change in intercellular CO2 concentration, transpiration rate and net photosynthetic rate of ‘Xingwang’ were higher than those of the diploid ‘S4’. The chlorophyll contents, the maximal photochemical efficiency of PSII and the potential photochemical efficiency of PSII in ‘Xingwang’ were higher than those of ‘S4’. The chloroplasts of ‘Xingwang’ contained thicker thylakoid lamellae. By the use of Illumina sequencing technology, a total of 51,807 unigenes were obtained; they had an average length of 1,487 nt, and the average N50 was 2,034 nt. The lengths of most of the unigenes obtained ranged from 200–300 bp, with an average value of 5,262, followed by those longer than 3,000 bp, with an average value of 4,791. The data revealed numerous differences in gene expression between the two transcriptomes. In total, 24,221 differentially expressed genes were screened, and the percentage of differentially expressed genes was as high as 46.75% (24,224/51,807), of which 10,474 genes were upregulated and 13,747 genes were downregulated. We analyzed the key genes in the photosynthesis pathway and the porphyrin and chlorophyll metabolism pathway; the upregulation of HemB may promote an increase in the chlorophyll contents of ‘Xingwang’, and the upregulation of related genes in PSII and PSI may enhance the light harvesting of ‘Xingwang’, increasing its light energy conversion efficiency. creator: Yi Wang creator: Bingyu Jia creator: Hongjian Ren creator: Zhen Feng uri: https://doi.org/10.7717/peerj.12620 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Wang et al. title: Spatiotemporal changes, trade-offs, and synergistic relationships in ecosystem services provided by the Aral Sea Basin link: https://peerj.com/articles/12623 last-modified: 2021-12-16 description: Intense human activities in the Aral Sea Basin have changed its natural distribution of land use. Although they provide certain economic benefits, these anthropogenic influences have led to the rapid shrinkage of the Aral Sea, severely affecting the region’s ecosystem. However, the spatiotemporal variability of the Aral Sea Basin’s Ecosystem Service Values (ESVs) is not well understood. In this study, we used 300-meter resolution land use maps from 1995, 2005, and 2015 and the Patch-generating Land Use Simulation (PLUS) model to predict the future land use patterns of the Aral Sea Basin in 2025. Simultaneously, we divided the Aral Sea Basin into three regions (upstream, midstream, and downstream) and evaluated the dynamic responses of their ESVs to Land Use and Land Cover (LULC) changes. The changes in the types of ecosystem services provided by the Aral Sea Basin, their trade-off, and synergistic relationships were analyzed by weighting their associations. The results showed that from 1995 to 2025, the grassland, urban, and cropland areas in the Aral Sea Basin will expand rapidly, while the areas covered by water bodies will shrink rapidly, causing a total loss of 31.97 billion USD. The downstream loss of 27.79 billion USD of the total amount is mainly caused by the conversion of water bodies to bare land. The ESVs of the middle region will increase by 6.81 billion USD, mainly due to the large amount of water extracted from the Amu Darya and Syr Darya Rivers in the middle regions of the Aral Sea Basin that are used to reclaim cultivated land and expand urban areas. The ESVs and areas experiencing land use changes in the upper regions are relatively small. At the same time, our results show that biodiversity, food production, and water regulation are the major ecosystem service functions, and account for 79.46% of the total ESVs. Of the ecosystem service relationships in the Aral Sea Basin, synergy accounts for 55.56% of the interactions, with a fewer amount of trade-off exchanges. This synergy mainly exists in the relationships involving water regulation, waste treatment and recreation, and culture and tourism. We propose protection measures that will coordinate eco-environmental protection efforts with socioeconomic development in the region in order to achieve the United Nations’ sustainable development goals. creator: Chao liang Chen creator: Xi Chen creator: Jing Qian creator: Zengyun Hu creator: Jun Liu creator: Xiuwei Xing creator: Duman Yimamaidi creator: Zhanar Zhakan creator: Jiayu Sun creator: Shujie Wei uri: https://doi.org/10.7717/peerj.12623 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Chen et al. title: Long-term follow-up of mandibular dental arch changes in patients with complete non-syndromic unilateral cleft lip, alveolus, and palate link: https://peerj.com/articles/12643 last-modified: 2021-12-16 description: BackgroundTreatment of cleft lip and palate (CLP) requires a comprehensive interdisciplinary approach and long-term follow-up. Only a few studies are available that reported on changes after treatment, which showed that in particular the transverse dimension, in patients with CLP is prone to changes after treatment. However, those studies did not pay attention to concomitant changes in the mandibular arch that occur after treatment.ObjectivesTo evaluate mandibular transverse dental arch dimensions and interarch transverse changes in patients with complete non-syndromic unilateral cleft lip, alveolus, and palate (CUCLAP) up to five years after treatment.Material and MethodsRetrospective longitudinal study in 75 consecutive patients with CUCLAP directly after comprehensive treatment (T0), two (T2), and 5 years after treatment (T5). Great Ormond Street, London and Oslo (GOSLON) scores were available for all patients. Three-dimensional scans of all dental casts were made. Inter premolar and intermolar distances between the mandibular contralateral teeth were measured. The modified Huddart Bodenham (MHB index) was applied to assess the transverse interarch relationship. Paired t-tests and ANOVA were used to analyze transverse and interarch transverse changes. Linear regression analysis was done to define contributing factors.ResultsPaired t-tests showed a significant decrease of the mandibular inter first and second premolar distances (p < 0.05) and an increase of the inter second molar distance, whilst the MHB Index deteriorated at all time points for all segments and for the total arch score (p < 0.05). Linear regression showed no significant contributing factors on the decrease of the transverse distances. However, inter arch transverse relationship was significantly affected by age at the end of treatment, missing maxillary lateral incisor space closure, and the GOSLON Yardstick score at the end of treatment (p < 0.05), especially during the first two years after treatment.ConclusionsChanges occurred in the mandibular arch expressed as changes in the transverse dimensions and interarch relationship measured by the MHB Index. A younger age at the end of treatment, space closure for a missing maxillary lateral incisor and a higher GOSLON score at the end of treatment negatively influence the interarch transverse deterioration especially in the first two years after treatment. For the transverse dimensional changes in the mandibular arch such influencing factors could not be determined. creator: Sariesendy Sumardi creator: Benny S. Latief creator: Anne Marie Kuijpers-Jagtman creator: Edwin M. Ongkosuwito creator: Ewald M. Bronkhorst creator: Mette A.R. Kuijpers uri: https://doi.org/10.7717/peerj.12643 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Sumardi et al. title: Putative fossil blood cells reinterpreted as diagenetic structures link: https://peerj.com/articles/12651 last-modified: 2021-12-16 description: Red to red-orange spheres in the vascular canals of fossil bone thin sections have been repeatedly reported using light microscopy. Some of these have been interpreted as the fossilized remains of blood cells or, alternatively, pyrite framboids. Here, we assess claims of blood cell preservation within bones of the therizinosauroid theropod Beipiaosaurus inexpectus from the Jehol Lagerstätte. Using Raman spectroscopy, Energy Dispersive X-ray Spectrometry, and Time of Flight Secondary Ion Mass Spectroscopy, we found evidence of high taphonomic alteration of the bone. We also found that the vascular canals in the bone, once purported to contain fossil red blood cell, are filled with a mix of clay minerals and carbonaceous compounds. The spheres could not be analyzed in isolation, but we did not find any evidence of pyrite or heme compounds in the vessels, surrounding bone, or matrix. However, we did observe similar spheres under light microscopy in petrified wood found in proximity to the dinosaur. Consequently, we conclude that the red spheres are most likely diagenetic structures replicated by the clay minerals present throughout the vascular canals. creator: Dana E. Korneisel creator: Sterling J. Nesbitt creator: Sarah Werning creator: Shuhai Xiao uri: https://doi.org/10.7717/peerj.12651 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Korneisel et al. title: Transcriptome analysis of ovary culture-induced embryogenesis in cucumber (Cucumis sativus L.) link: https://peerj.com/articles/12145 last-modified: 2021-12-15 description: Background.Ovary culture is a useful technique used to generate double haploid (DH) cucumber (Cucumis sativus L.) plants. However, cucumber ovary culture have a low rate of embryo induction and plant regeneration. Moreover, the cucumber embryogenesis mechanism remains unclear. In this study, we explored the molecular basis of cucumber embryogenesis in order to establish a foundation for a more efficient ovary culture method. Using transcriptome sequencing, we also investigated the differential expression of genes during the embryogenesis process.Methods.Cytological and morphological observations have divided cucumber ovary culture into three stages: early embryo development (T0), embryo morphogenesis (T1, T2, T3 and T4), and shoot formation (T5). We selected six key time points for transcriptome sequencing and analysis: T0 (the ovules were cultured for 0 d), T1 (the ovules were cultured for 2 d), T2 (the embryos were cultured for 10 d), T3 (the embryos were cultured for 20 d), T4 (the embryos were cultured for 30 d), and T5 (the shoots after 60 d culture).Results.We used cytology and morphology to observe the characteristics of the cucumber’s developmental transformation during embryogenesis and plant regeneration. The differentially expressed genes(DEGs) at developmental transition points were analyzed using transcriptome sequencing. In the early embryogenesis stage, the cells expanded, which was the signal for gametophytes to switch to the sporophyte development pathway. RNA-seq revealed that when compared to the fresh unpollinated ovaries, there were 3,468 up-regulated genes in the embryos, including hormone signal transduction genes, hormone response genes, and stress-induced genes. The reported embryogenesis-related genes BBM, HSP90 and AGL were also actively expressed during this stage. In the embryo morphogenesis stage (from cell division to cotyledon-embryo formation), 480 genes that functioned in protein complex binding, microtubule binding, tetrapyrrole binding, tubulin binding and other microtubule activities were continuously up-regulated during the T1, T2, T3 and T4 time points. This indicated that the cytoskeleton structure was continuously being built and maintained by the action of microtubule-binding proteins and enzyme modification. In the shoot formation stage, 1,383 genes were up-regulated that were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, phenylalanine metabolism, and starch and sucrose metabolism. These up-regualted genes included six transcription factors that contained a B3 domain, nine genes in the AP2/ERF family, and two genes encoding WUS homologous domain proteins.Conclusions.Evaluation of molecular gynogenesis events may contribute to a better understanding of the molecular mechanism of cucumber ovarian culture. creator: Ying Deng creator: Wenyuan Fu creator: Bing Tang creator: Lian Tao creator: Lu Zhang creator: Xia Zhou creator: Qingqing Wang creator: Ji Li creator: Jinfeng Chen uri: https://doi.org/10.7717/peerj.12145 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2021 Deng et al.